This proposal attempts to determine the biologic importance and therapeutic potential of a more thorough understanding of autacoids as immune modulators in man. There are two cornerstones of this proposal: 1) the observation that some mediators of inflammation may modulate immunity; and 2) that chemical modification of selected mediators of inflammation (histamine and catecholamines) can result in formation of tissue and effect specific immune modulators. Furthermore, it is becoming evident in studies of mouse systems that sources of histamine may be within lymphocytes in addition to mast cells; that release mechanisms for histamine may be complex but controllable and organized; that receptors for the two autacoids mentioned are non-randomly distributed on subsets of lymphyocytes; that expression of autacoid effects are dependent on the lymphocytic cells in the environment and the stage of immune response; and that the effects of autacoids on subsets of cells and their physiologic interactions are possible. The proposed study attempts to: 1) determine whether the data from mice can be extrapolated and extended to man by using human cells in vitro and both histamine and catecholamines as well as their congeners and conjugates as experimental probes; and 2) to set the stage for determining the appropriateness and feasibility of using congeners and conjugates of autacoids as therapeutic immune modulators.
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